At least four loci and gender are associated with susceptibility to the chemical induction of lung adenomas in A/J x BALB/c mice

• Published in: Genomics (San Diego, Calif.) Vol. 53; no. 2; pp. 129 - 136
• Main Authors: FESTING, M. F. W, LIN, L, DEVEREUX, T. R, GAO, F, YANG, A, ANNA, C. H, WHITE, C. M, MALKINSON, A. M, YOU, M
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier 15.10.1998
• Subjects: Adenoma - chemically induced; Adenoma - genetics; Animals; Biological and medical sciences; Chromosome Mapping; Classical genetics, quantitative genetics, hybrids; Crosses, Genetic; Female; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Lod Score; Lung Neoplasms - chemically induced; Lung Neoplasms - genetics; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred Strains - genetics; Microsatellite Repeats; Quantitative Trait, Heritable; Sex Factors; Urethane - toxicity; Vertebrata; Genetic mapping; Lung disease; Animal model; Respiratory disease; Induction; Quantitative character; Lung; Rodentia; Sex; Chromosome; Adenoma; Urethane; Carcinogenesis; Vertebrata; Mammalia; Mouse; Risk factor; Benign neoplasm; Genetic association
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1998.5450

Four putative quantitative trait loci (QTLs) that influence susceptibility to the induction of lung adenomas by urethane in an F2 cross between A/J and BALB/cOlaHsd have been mapped. Following microsatellite typing of mice with resistant and susceptible phenotypes at 97 microsatellite marker loci, a major locus was identified on chromosome 18 with a lod score of 15. This was responsible for an 8- to 10-fold increase in tumor multiplicity in males and females, respectively, having the AA and CC genotypes at the D18Mit188 marker locus. It mapped close to Dcc (deleted in colorectal cancer). A locus on chromosome 4 (lod score 6.5) had the resistant allele in strain A/J and the susceptible allele in BALB/c, with a 14-fold difference in tumor multiplicity between mice of the AA and CC genotypes. This mapped close to the Cdkn2a (cyclin-dependent kinase inhibitor 2A) locus, which is commonly deleted in mouse lung tumors. Two loci with smaller effects (lod scores 3.03 and 3.25) were identified on chromosomes 1 and 11. There was also significant sexual dimorphism in tumor multiplicity both among 151 F2 hybrids and among 52 mice resulting from a backcross to strain A/J, with males having higher tumor counts than females.